The present invention is directed to novel pharmaceutical compositions having antihypertensive activity. The compositions comprise (a) an aryl substituted alanine and (b) a substituted phenyl hydrazino propionic acid decarboxylase inhibitor.
3-cyano-.alpha.-methylphenylalanine methyl ester PA0 4-cyanoamino-.alpha.-methylphenylalanine PA0 3-carboxy-.alpha.-methylphenylalanine PA0 .alpha.-methyl-4-thiocarbamoylphenylalanine methyl ester PA0 4-(aminomethyl)-.alpha.-methylphenylalanine PA0 4-guanidino-.alpha.-methylphenylalanine PA0 3-hydroxy-4-methanesulfonamido-.alpha. -methylphenylalanine PA0 3-hydroxy-4-nitro-.alpha.-methylphenylalanine PA0 4-amino-3-methanesulfonyloxy-.alpha.-methylphenylalanine PA0 3-carboxymethoxy-4-nitro-.alpha.-methylphenylalanine PA0 4-amino-.alpha.-methyl-3-nitrophenylalanine PA0 3,4-diamino-.alpha.-methylphenylalanine PA0 .alpha.-methyl-4-(pyrrol-1-yl)phenylalanine PA0 4-(2-aminoimidazol-1-yl)-.alpha.-methylphenylalanine PA0 4-(imidazol-2-ylamino)-.alpha.-methylphenylalanine PA0 4(4,5-dihydro-4-hydroxy-4-trifluoromethyl-thiazol-2-yl)-.alpha.-methylpheny lalanine methyl ester PA0 .alpha.-methyl-4-(4-trifluoromethylthiazol-2-yl)phenylalanine PA0 .alpha.-methyl-3-(4-trifluoromethylthiazol-2-yl)-phenylanaline PA0 4-(imidazol-2-yl)-.alpha.-methylphenylalanine PA0 4-(4,5-dihydroimidazol-2-yl)-.alpha.-methylphenylalanine PA0 3-(imidazol-2-yl)-.alpha.-methylphenylalanine PA0 3-(4,5-dihydroimidazol-2-yl)-.alpha.-methylphenylalanine PA0 4-(imidazol-2-yl)phenylalanine PA0 4-(4,5-dihydroimidazol-2-yl)phenylalanine PA0 3-(imidazol-2-yl)phenylalanine PA0 3-(2,3-dihydro-1 H-indol-4-yl)-.alpha.-methylalanine PA0 .alpha.-methyl-3-(1 H-2-oxindol-5-yl)alanine PA0 3-[1-(N-benzoylcarbamimidoyl)-2,3-dihydro-1 H-indol-5-yl)] -.alpha.-methylalanine PA0 3-(1-carbamimidoyl-2,3-dihydro-1 H-indol-5-yl)-.alpha.-methylalanine PA0 3-(1 H-indol-5-yl)-.alpha.-methylalanine PA0 3-(benzimidazol-2-thione-5-yl)-.alpha.-methylalanine PA0 3-(2-aminobenzimidazol-5-yl)-2-methylalanine PA0 2-methyl-3-(benzoxazol-2-on-6-yl)alanine PA0 3-(2-aminobenzothiazol-6-yl)-2-methylalanine PA0 3-(2-amino-4-mercaptobenzothiazol-6-yl)-2-methylalanine PA0 3-(2-aminobenzothiazol-6-yl)alanine PA0 2-methyl-3-(2,1,3-benzothiadiazol-5-yl)-alanine PA0 3-(1,3-dihydrobenzo-2,1,3-thiadiazol-5-yl)-2-methylalanine-2,2-dioxide PA0 3-(1,3-dihydrobenzo-2,1,3-thiadiazol-5-yl)-2-methylalanine-2,2-dioxide methyl ester PA0 3-(1,3-dihydrobenzo-2,1,3-thiadiazol-5-yl)-alanine 2,2-dioxide PA0 3-(1,3-dihydro-1,3-dimethylbenzo-2,1,3-thiadiazol-5-yl)-2-methylalanine 2,2-dioxide PA0 .alpha.-methyl-3-[4-methyl-2(1H)-oxoquinolin-6-yl]alanine PA0 3-[4-methyl-2(1 H)-oxoquinolin-6-yl]alanine PA0 2-methyl-3-(quinoxalin-6-yl)alanine PA0 2-methyl-3-(2-hydroxyquinoxalin-6-yl)alanine PA0 2-methyl-3-(2-hydroxyquinoxalin-7-yl)alanine PA0 3-(2,3-dihydroxyquinoxalin-6-yl)-2-methylalanine PA0 3-(quinoxalin-6-yl)alanine PA0 3-(2,3-dihydroxyquinoxalin-6-yl)alanine PA0 3-(1,4-benzoxazin-3-one-6-yl)-2-methylalanine PA0 3-(1,4-benzoxazin-3-one-7-yl)alanine PA0 3-(5-hydroxy-4 H-pyran-4-on-2-yl)-2-methylalanine PA0 3-(2-hydroxy-4-pyridyl)-2-methylalanine PA0 3-(2-carboxy-4-pyridyl)-2-methylamine PA0 3-formyl-.alpha.-methyltyrosine PA0 3-cyano-.alpha.-methyltyrosine PA0 3-carboxy-.alpha. -methyltyrosine PA0 .alpha.-methyl-4-(pyrrol-1-yl)phenylalanine PA0 .alpha.-methyl-4-(pyrrol-1-yl)phenylalanine PA0 .alpha.-methyl-4-(pyrrol-1-yl)phenylalanine PA0 4-[2-(carboxy)pyrrol-1-yl]phenylalanine PA0 .alpha.-methyl-4-pyrrol-1-yl)phenylalanine PA0 3-hydroxy-.alpha.-methyl-4-(pyrrol-1-yl)phenylalanine PA0 3-methoxy-.alpha.-methyl-4-(pyrrol-1-yl)phenylalanine PA0 .alpha.-methyl-3-(pyrrol-1-yl)tyrosine PA0 4-methoxy-.alpha.-methyl-3-(pyrrol-1-yl)phenylalanine PA0 4-(indol-1-yl)-.alpha.-methylphenylalanine PA0 4-carbazol-9-yl)-.alpha.-methylphenylalanine PA0 .alpha.-methyl-3-(4-trifluoromethylthiazol-2-yl)tyrosine PA0 3-(imidazol-2-yl)-.alpha.-methyltyrosine PA0 2-methyl-3-(2-methanesulfonylamidobenzimidazol-5-yl)alanine PA0 2-methyl-3-(2-amino-4-pyridyl)alanine PA0 2-methyl-3[tetrazolo(1,5-.alpha.)-pyrid-7-yl]alanine PA0 D,l-4-cyanoamino-.alpha.-methylphenylalanine PA0 D,l-4-guanidino-.alpha.-methylphenylalanine PA0 D,l-3-hydroxy-4-methanesulfonamido-.alpha.-methylphenylalanine PA0 D,l-4-amino-3-methanesulfonyloxy-.alpha.-methylphenylalanine PA0 D,l-4-(2-aminoimidazol-1-yl)-.alpha.-methylphenylalanine and D,L-4-(imidazol-2-yl-amino)-.alpha.-methylphenylalanine PA0 D,l-4-(imidazol-2-yl)-.alpha.-methylphenylalanine PA0 D,l-4-(4,5-dihydroimidazol-2-yl)-yl)-.alpha.-methylphenylalanine PA0 D,l-2-methyl-3-(benzoxazol-2-on-6-yl)alanine PA0 D,l-3-(2-amino-4-mercaptobenzothiazol-6-yl)-2-methylalanine PA0 D,l-3-(1,3-dihydrobenzo-2,1,3-thiadiazol-5-yl)-2-methylalanine 2,2-dioxide PA0 D,l-3-(1,3-dihydrobenzo-2,1,3-thiadiazol-5-yl)-2-methylalanine 3,3-dioxide methyl ester PA0 D,l-3-(1,3-dihydrobenzo-2,1,3-thiadiazol-5-yl)-alanine 5,5-dioxide PA0 D,l-3-(1,3-dihydro-1,3-dimethylbenzo-2,1,3-thiadiazol-5-yl)-2-methylalanine 2,2-dioxide PA0 D,l-2-methyl-3-(quinoxalin-6-yl)alanine dihydrochloride PA0 D,l-3-(quinoxalin-6-yl)alanine PA0 D,l-3-(2,3-dihydroxyquinoxalin-6-yl)alanine hydrochloride PA0 D,l-3-(5-hydroxy-4 H-pyran-4-on-2-yl)-2-methylalanine PA0 D,l-3-(2-hydroxy-4-pyridyl)-2-methylalanine PA0 .alpha.-hydrazino-.beta.-3,4-dihydroxyphenylpropionic acid methyl ester, PA0 .alpha.-hydrozino-.alpha.-methyl-.beta.-3,4-dihydroxyphenylpropionic acid butyl ester PA0 .alpha.-hydrazino-.beta.-3,4-dihydroxyphenylpropionic acid, PA0 .alpha.-hydrazino-.beta.-3,4-dibutoxyphenylpropionic acid, PA0 .alpha.-hydrazino-.beta.-3,4-dimethoxyphenylpropionic acid, PA0 .alpha.-hydrazino-.alpha.-butyl-.beta.-3,4-dihydroxyphenylpropionic acid, PA0 .alpha.-hydrazino-.alpha.-ethyl-.beta.-3,4-dihydroxyphenylpropionic acid, PA0 .alpha.-hydrazino-.alpha.-.beta.-3,4-dimethoxyphenylpropionic acid and the like.
Hydroxyphenylalanines and derivatives thereof are disclosed in U.S. Pat. No. 2,868,818; U.S. Pat. No. 3,230,143 and U.S. Pat. No. 3,344,023. Benzimidazolylalanines are disclosed in J. Med. Chem. 17, 1223-1225 (1974), J. Med. Chem. 13, 741-742 (1970), and Abstract No. 964 of the Fifth International Congress on Pharmacology, July 23-28, 1972. The hydrazino substituted phenyl propionic acid class of decarboxylase inhibitors is also disclosed in the art. (See U.S. Pat. No. 3,462,536; 3,781,415 and 3,820,827). The combination of certain compounds, including hydroxyphenylalanines with decarboxylase inhibitors of this class is disclosed in the art. (Canadian Pat. No. 737,907, U.S. Pat. Nos. 3,839,585 and 3,462,536).
It has been discovered that novel aryl alanines and their esters in combination with the aforesaid decarboxylase inhibitors have enhanced antihypertensive activity.